This patent is directed to a pharmaceutical product and method of use thereof, and in particular to an pharmaceutical product and method of use thereof for halogenated anesthetics.
It is well known to use machines, known as vaporizers, to convert anesthetics from a liquid form to a gaseous form that may be administered to a patient. The liquid anesthetic is typically stored in a bottle-type container. In use, the container is mated with a port on the vaporizer, and the liquid is transferred from an interior chamber of the container to a reservoir in the vaporizer. The liquid anesthetic is then vaporized and mixed with oxygen (and optionally other gases). The gaseous mixture may then be administered to the patient.
A number of different materials have been used to manufacture the container for use with such anesthetics.
Glass has been the traditional material of choice. Of course, glass presents certain challenges. Glass requires careful handling to avoid breakage, and when breakage does occur, product is lost and injury may occur. Additionally, U.S. Pat. No. 5,990,176 theorizes that certain halogenated inhalation anesthetics may react with components of the glass, causing the anesthetic to degrade. In particular, it is hypothesized that the aluminum oxides in the glass act as Lewis acids in the reaction that degrades the anesthetics.
In the alternative, certain plastics have been suggested for use in containers for storing halogenated anesthetics, such as sevoflurane. For example, U.S. Pat. No. 4,250,334 illustrates use of “Kel-F” plastic (“Kel-F” understood to be the trade name for polychlorotrifluoroethylene) to make a container for holding sevoflurane. U.S. Pat. No. 5,679,576 illustrates a container lined with polytetrafluoroethylene (PTFE) for holding sevoflurane. Similarly, the following patents illustrate plastic containers for sevoflurane: U.S. Pat. No. 6,074,668 (polyethylene napthalate); U.S. Pat. No. 6,083,514 (polymethylpentene); U.S. Pat. No. 6,162,443 (polypropylene, polyethylene and ionomeric resins); and U.S. Pat. No. 6,558,679. U.S. Pat. No. 5,505,236 also teaches the use of thermoplastic containers with liquid inhalation agents.
While plastic containers are less likely to break than glass containers, the containers are still susceptible to breakage under common use conditions. Moreover, many plastics tend to be vapor permeable, which may allow the inhalation anesthetic to escape the container over time. Vapor permeability also permits ambient vapors to enter the container, leading to possible contamination and/or change in the water content of the formulation. For that matter, inhalation anesthetics have strong organic solvent properties, and thus could cause the plastic to dissolve and/or to react, leading to measurable impurities in the inhalation anesthetic. Further, plastic containers are subject to deformation when exposed to elevated temperatures, which temperatures may be required during processing and treatment of the containers.
As a still further alternative, some have suggested use of metal containers. For example, U.S. Pat. No. 5,990,176 describes containers for sevoflurane made of stainless steel, glass or plastic for holding sevoflurane. A more recent discovery has been the use of aluminum to make containers for anesthetics such as sevoflurane, desflurane, isoflurane, enflurane, methoxyflurane and halothane. In particular, it has been suggested that aluminum containers be used, either unlined or lined with an enamel or a lacquer, which enamel or lacquer may include an epoxy-phenolic resin. See U.S. Publ. No. 2002/0068767.
On the other hand, it has been suggested that certain metals would not be acceptable for use in a container for anesthetics, and in particular halogenated anesthetics. See U.S. Publ. No. 2008/0087283. In particular, it is stated that degradation of sevoflurane has been observed in glass containers, and that the degradation is believed to be activated by trace amounts of Lewis acids present in the container. While aluminum oxide is identified in U.S. Publ. No. 2008/0087283 as one source for Lewis acids, it is stated therein that there are other “oxidizing” metals that would similarly provide Lewis acids. In particular, nickel and nickel alloys are identified as exemplary oxidizing metals.
As set forth in more detail below, the present disclosure sets forth an improved system embodying advantageous alternatives to the conventional systems and methods discussed above.